Professor Lu Aiping (second from right), Dr Zhang Ge (right), Dr Li Defang (second from left), and Mr Liu Jin are delighted that their research provides a new target for osteoporosis treatment in elderly women


呂愛平院長 (右二)、張戈博士 (右)、李德芳博士 (左二) 與劉進同學高興研究為治療女性老年骨質疏鬆症提供了新靶點

Date: 16 Mar 2016 (Wednesday)

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HKBU Chinese medicine study, published in Nature Communications, discovers new target for osteoporosis treatment in elderly women

浸大中醫藥學院發現治療女性老年骨質疏鬆症的新靶點 研究論文於《Nature Communications》雜誌發表

A research team from the School of Chinese Medicine (SCM) recently conducted a study on osteoporosis in elderly women. It was found that the decreased bone formation has a close correlation with osteoblastic activity and the osteoclast-secreted exosomal miR-214-3p in elderly women with osteoporosis. This study not only provided a new understanding of the pathogenesis of osteoporosis induced by age-related bone loss in elderly women, but also supplied a novel strategy and new target for osteoporosis treatment. The results have been published online in the highly reputed journal Nature Communications,
March 2016 issue (http://www.nature.com/ncomms/2016/160307/ncomms10872/full/ncomms10872.html).

Co-corresponding authors of the paper are Professor Lu Aiping, Dean of SCM and Director of the Institute for Advancing Translational Medicine in Bone & Joint Diseases (TMBJ), and Dr Zhang Ge, Associate Director of the Teaching and Research Division of SCM, Director of the Technology Development Division of SCM, and Associate Director of TMBJ, who are also jointly in charge of the study. Meanwhile, Dr Li Defang, Research Assistant Professor and Mr Liu Jin, PhD student who have contributed equally were listed as co-first authors.

Professor Lu Aiping said that the dynamic equilibrium between osteoclasts and osteoblasts is an important factor for maintaining the integrity of skeletal structure, which is comparable to the balance of yin and yang advocated by traditional Chinese medicine. The strengthening or weakening of either cells will cause an imbalance of yin and yang, leading to the occurrence of skeletal diseases. The researchers found that the elevated miR-214-3p within osteoclasts could be secreted in exosome-encapsulated form and inhibits the activity of osteoblasts, resulting in bone loss.

Dr Zhang Ge mentioned that in order to further confirm whether miR-214-3p was involved in the signal transduction between osteoclasts and osteoblasts, the multi-disciplinary research team not only designed osteoclast-specific miR-214-3p knock-in mice, but also used the osteoclast-targeted delivery system constructed by the research team to deliver miR-214-3p antagonist (antagomir-214-3p) to osteoclasts. The above experiments were performed to determine the effect of miR-214-3p on bone formation through increasing or reducing the miR-214-3p.

Dr Li Defang and Mr Liu Jin indicated that miR-214-3p could be considered as a target for the treatment of skeletal diseases which result in bone loss. Their next step is to search for potential therapeutic natural products to help elderly women with osteoporosis. The research team will use molecular docking to screen the targeted inhibitor of miR-214-3p or the upstream transcription factor from the compound database of Chinese herbal medicine in the School of Chinese Medicine.
   
This multi-disciplinary study involves many HKBU scholars, including Professor Chris Wong from the Department of Biology, Professor Bian Zhaoxiang, Dr Yang Zhijun, Dr Zhu Hailong and Dr Guo Baosheng from the School of Chinese Medicine, researchers from the University’s Institute of Integrated Bioinformedicine and Translational Science, HKBU Institute of Research and Continuing Education, and HKBU (Haimen) Institute of Science and Technology.

中醫藥學院的研究團隊最近完成一項有關老年骨質疏鬆症的研究,發現女性老年化骨質疏鬆患者的成骨能力下降,與患者體內成骨細胞的活性程度和破骨細胞分泌的外來體包裹的miR-214-3p有著重要的關聯。該研究不僅為成骨能力下降誘發的老年性骨質疏鬆發病機制提出了新觀點,亦為有關治療提供了新策略與新靶點。研究結果於2016年3月在國際著名科學雜誌《Nature Communications》網上發表(http://www.nature.com/ncomms/2016/160307/ncomms10872/full/ncomms10872.html)。

該研究項目由浸大中醫藥學院院長兼骨與關節疾病轉化醫學研究所所長呂愛平教授,與中醫藥學院教學科研部副主任、研究開發部主任兼骨與關節疾病轉化醫學研究所副所長張戈博士聯合負責,並擔任論文的共同通訊作者,論文的共同第一作者為學院的研究助理教授李德芳博士和博士研究生劉進同學。

呂愛平教授認為,破骨細胞與成骨細胞之間的動態平衡是維持骨骼結構完整的重要因素,正如傳統中醫所提倡的陰陽平衡,任何一方的增強或減弱都將發生陰陽失衡,從而導致疾病的發生。研究人員發現在女性老年化骨質疏鬆症患者骨組織中,破骨細胞內高表達的miR-214-3p,可通過外來體包裹的形式分泌到細胞外,抑制了成骨細胞的活性,從而導致了成骨能力下降。

張戈博士指出,為了進一步確認miR-214-3p是否參與了破骨細胞與成骨細胞之間的信號轉導,聯合研究團隊成員不僅設計了破骨細胞特異性高表達miR-214-3p的轉基因小鼠實驗,還利用了團隊構建的破骨細胞靶向遞送系統進行實驗,將miR-214-3p拮抗劑(antagomir-214-3p)遞送到破骨細胞內,從而升高或降低破骨細胞內的miR-214-3p,確定其對成骨能力的影響。

李德芳博士和劉進同學表示,研究顯示miR-214-3p可作為成骨能力下降相關骨骼疾病的治療靶點,研究團隊下一步將利用分子對接技術,從學院的中藥化合物數據庫虛擬篩選出miR-214-3p或其上游轉錄因數的靶向抑制劑,藉此尋找出具有治療老年化骨質疏鬆症潛能的天然產物分子化合物。

這次研究亦是一項多學科合作項目,得到多位浸大學者參與,包括生物系的黃港住教授、中醫藥學院的卞兆祥教授、楊智鈞博士、祝海龍博士、郭保生博士,以及來自浸大整合生物信息醫學與轉化科學研究所、浸大深圳研究院、浸大(海門)科技研究院等單位的研究人員。